Abstract 9717: Hypertension-Induced Atrial Remodeling Promotes Atrial Fibrillation Stabilization Upon Tachyarrhythmia Onset
Background: Hypertension (HT) is a major risk factor for atrial fibrillation (AF) but the underlying mechanisms are poorly understood. We hypothesized that HT produces an AF-stabilizing influence that favors faster progresion of spontaneous AF-maintenance when atrial tachyarrhythmia (AT) begins.
Methods: HT was induced in dogs (n=6) by left nephrectomy and right renal artery constriction (1K1C). Sham operated dogs with the same surgery but no nephrectomy or artery constriction (n=5) were controls. Beginning 28 days from surgery, AT-pacing (ATP, 600 bpm) was started for 7 days. Serial atrial ERP measurement and AF induction was performed at days 7, 14, 28, 29, 30, 32 and 35 from surgery. Final open chest EPS was performed at day 36.
Results: Systolic blood pressure (SBP) of HT dogs increased beginning at day 7 post 1K1C surgery (baseline 128±4 mm Hg; 7-d 183±6*, 28-d 176±10* mmHg; * p<0.01 vs. baseline). SBP of sham dogs remained constant (baseline 133±4 mm Hg; 7-d 128±3, 28-d 126±6 mmHg). Mean AF duration (10 Hz burst pacing induced) increased marginally in HT dogs pre-ATP (Figure), but substantially after 1 and 2 days ATP vs control. At open-chest EPS, there were no differences in AF vulnerability to premature extrastimuli (HT, 69±5% vs. Sham, 70±11%; p=NS), AF duration (HT, 1501±273 sec vs. Sham, 1458±342 sec; p=NS) or regional ERP heterogeneity. HT dogs showed increased atrial conduction heterogeneity (heterogeneity index in HT, 2.01±0.10 vs. sham, 1.50±0.08; p<0.01), associated with significant downregulation of connexin (Cx) 43 expression (by 57%+, +p<0.05) but no change in Cx40 expression. Heart to body weight ratio increased in HT (9.7±0.4 vs. 8.5±0.2+), reflecting LVH.
Conclusions: HT alone produces modest AF promotion, but changes caused by HT accelerate AF stabilization once initiated, increasing vulnerability to prolonged AF. The AF-promoting effects of hypertension are related to conduction abnormalities, possibly caused by connexin downregulation.
- © 2011 by American Heart Association, Inc.